Multiscale Biomarkers in PANDAS: From Neuroimaging Studies to the Immunological

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a relatively newly defined disorder that affects children who have experienced an untreated Group A Beta-Hemolytic Streptococcus (GABHS) infection. This mini-narrative review synthesizes current evidence of candidate biomarkers for PANDAS and their potential to improve diagnostic, prognostic, and therapeutic methods. A literature search was conducted through PubMed for articles in English pertaining to PANDAS, including studies related to pediatric acute-onset neuropsychiatric syndrome (PANS). Additionally, reference lists from included studies were considered to identify additional eligible publications. The results included articles that utilized neuroimaging techniques and immunological data from patient sera and cerebrospinal fluid data. Across methodologies, converging evidence supports immune-related dysfunction with specific findings of basal ganglia involvement. Small samples, heterogeneous methods, and sensitivity to age and disease stage are factors that may limit clinical adoption of these biological criteria. Overall, this review provides evidence that, where specific immune mechanisms can be documented, diagnostic blood tests and targeted therapies may be beneficial, though evidence remains limited. We outline proposal priorities for future studies, including longitudinal designs along with the use of classification models to establish diagnostic and/or prognostic utility.